Cancer
Being well-prepared for battle engenders success; when the foe is cancer, early detection results in a greater likelihood that medical intervention will be successful. At early stages, treatments can often be targeted only to the affected tissues, diminishing side effects. If not caught early, cancer cells may metastasize and spread throughout the body. The prognosis in this case is more dire, and medical treatments are often applied systemically, killing not only cancer cells, but large numbers of healthy cells.
The National Cancer Institute estimates that in 2002, 1.285 million Americans will be newly diagnosed with cancer, and more than 560,000 Americans will die from of cancer related illness.
A hallmark of a cancer cell is uncontrolled proliferation. Uncontrolled proliferation of these cells can manifest as cell masses (tumors) that interfere with normal organ function. If proliferation is not controlled or contained, cells from tumors migrate and colonize other tissues of the body, eventually resulting in death.
External factors, such as tobacco smoke, radiation and viruses, can lead to alterations in specific genes that result in unregulated cellular proliferation. Intrinsic factors, including inheritable mutations, hormone levels and metabolism, contribute to one's risk of contracting cancer.
Cancer cells also exhibit morphological and functional aberrations. Cellular morphology may be less organized; for example, the cells losing the asymmetric organelle and structural organization (cell polarity) that allows for proper cell function. Cell-cell and cell-substratum contacts, the specificities of which are also necessary for normal function, are often modulated or lost. Functionally, the cells may carry on few, if any, wild-type functions, or may have exaggerated, unregulated normal functions, such as hormone secretion. Such cells regress to early developmental stages, appearing less differentiated than their wild-type (i.e., normal) parents.
Cancer cells also often mis-express or mis-target proteins to inappropriate cellular compartments. Proteins may be up- or down-regulated; even proteins not usually expressed by a specific cell type can be expressed by the transformed counterpart. Protein mis-expression can have a plethora of downstream cellular effects, including drastic changes in membrane composition, organelle formation, or physiology. Mis-targeting of proteins (and other molecules, such as lipids, etc.) also contributes to the loss of cell polarity.
Treatments for Cancer
Methods for treating cancers include surgery (physical removal of the cancerous tissues), radiation therapy (killing cells by exposure to cell-lethal doses of radioactivity), chemotherapy (administering chemical toxins to the cells), immunotherapy (using antibodies that target cancer cells and mark them for destruction by the innate immune system) and nucleic acid-based therapies (e.g., expression of genetic material to inhibit cancer growth). Each approach, however, has its limitations.
Surgery, chemotherapy and radiation therapy suffer from similar significant limitations, such as incomplete removal of cancer cells or the inadvertent killing of healthy cells. Surgical tactics are most effective when the cancers are in early stages and limited localized area in the body. Even in the few cases that are diagnosed early, surgical removal of cancerous cells is often incomplete, and re-emergence of metastatic lesions often follow. When chemotherapeutic agents are administered in precise doses, they are preferentially toxic to rapidly proliferating cancer cells and not injuring the majority of healthy cells. Locally delivered doses of external beam radiation are most effective on rapidly growing cells, killing them by introducing non-specific, DNA-damage. Radiation therapy, like surgery, works best when the targeted cancer mass is well delimited; the balance of killing healthy cells versus cancer cells must be carefully weighed. Both chemotherapy and radiation therapy are not entirely selective for cancerous cells; inevitably, some healthy cells fall victim to the toxic effects, inflicting profound side-effects on the already-suffering cancer victim.
Other common approaches, immunotherapy and gene therapy, can be quite powerful and surpass surgery, chemo- and radiation therapy. These techniques target specific factors that are associated with tumor survival, cell growth or metastasis. For example, antibodies can target specific tumor-associated proteins, such as the monoclonal antibody that binds to a surface protein specific to the B-cells, CD20 (RITUXAN®; Genentech, Inc. and IDEC Inc.) that is used to treat B-cell malignancies. An example of an effective gene therapy is anti-sense inhibition of bcl-2 expression (GENASENSE®; Genta, Inc.). While effective, the challenge is to identify those clinically relevant genes and proteins and develop appropriate therapeutics that target them to result in the destruction of the cancer cell. Furthermore, the process is not only laborious in identifying these molecules, but in many instances, the identified molecules will be specific to only one type of cancer or tumor cell.